The human immunodeficiency virus (HIV) is a pathogenic retrovirus (Varmus, H. (1988) “RETROVIRUSES,” Science 240:1427-1439; Cowley S. (2001) “THE BIOLOGY OF HIV INFECTION” Lepr Rev. 72(2):212-20). HIV-1 is the causative agent of acquired immune deficiency syndrome (AIDS) and related disorders (Gallo, R. C. et al. (1983) “Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS),” Science 220(4599):865-7; Barre-Sinoussi, F. et al. “ISOLATION OF A T-LYMPHOTROPIC RETROVIRUS FROM A PATIENT AT RISK FOR ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS),” (1983) Science 220:868-870; Gallo, R. et al. (1984) “FREQUENT DETECTION AND ISOLATION OF CYTOPATHIC RETROVIRUSES (HTLV-III) FROM PATIENTS WITH AIDS AND AT RISK FOR AIDS,” Science 224:500-503; Teich, N. et al. (1984) “RNA TUMOR VIRUSES,” Weiss, R. et al. (eds.) Cold Spring Harbor Press (NY) pp. 949-956).
Since 1987, more than 25,000 individuals have received immunizations with human immunodeficiency virus (HIV) preventive vaccines. Currently, most of the HIV vaccine candidates are complex products containing multiple viral genes or proteins. Prime-boost strategies are under way to optimize cellular and humoral immune responses. Consequently, vaccine recipients' sera are often reactive in licensed HIV serodetection assays, generating patterns indistinguishable from HIV-infected individuals (Ackers, M. L. et al. (2003) “HUMAN IMMUNODEFICIENCY VIRUS (HIV) SEROPOSITIVITY AMONG UNINFECTED HIV VACCINE RECIPIENTS,” J Infect Dis 187:879-986; Pitisuttithum, P. et al. (2003) “SAFETY AND IMMUNOGENICITY OF COMBINATIONS OF RECOMBINANT SUBTYPE E AND B HUMAN IMMUNODEFICIENCY VIRUS TYPE 1 ENVELOPE GLYCOPROTEIN 120 VACCINES IN HEALTHY THAI ADULTS,” J Infect Dis 188:219-227; Chuenchitra, T. et al. (2003) “LONGITUDINAL STUDY OF HUMORAL IMMUNE RESPONSES IN HIV TYPE 1 SUBTYPE CRF01_AE (E)-INFECTED THAT PATIENTS WITH DIFFERENT RATES OF DISEASE PROGRESSION,” AIDS Res Hum Retroviruses 19:293-305; Schwartz, D. H. et al. (1995) “UTILITY OF VARIOUS COMMERCIALLY AVAILABLE HUMAN IMMUNODEFICIENCY VIRUS (HIV) ANTIBODY DIAGNOSTIC KITS FOR USE IN CONJUNCTION WITH EFFICACY TRIALS OF HIV-1 VACCINES,” Clin Diagn Lab Immunol 2, 268-271). This will have a negative impact on future prophylactic vaccine trials, in which early detection of HIV infections is of paramount importance. Furthermore, long-term HIV seropositivity will exclude vaccine trial participants from the pool of blood and plasma donors, and will contribute to a plethora of socio-economic harms including denied employment, health insurance, travel, immigration, and recruitment to the armed forces (Belshe, R. B. et al. (1994) “INTERPRETING HIV SERODIAGNOSTIC TEST RESULTS IN THE 1990S: SOCIAL RISKS OF HIV VACCINE STUDIES IN UNINFECTED VOLUNTEERS,” NIAID AIDS Vaccine Clinical Trials Group. Ann Intern Med 121:584-589; Allen, M. et al. (2001) “TRIAL-RELATED DISCRIMINATION IN HIV VACCINE CLINICAL TRIALS. AIDS RES HUM RETROVIRUSES,” 17:667-674). Therefore, the prospect of seroconversion could deter potential trial participants and severely curtail recruitment into large scale trials around the globe (Gross, M. et al. (1996) “INTEREST AMONG GAY/BISEXUAL MEN IN GREATER BOSTON IN PARTICIPATING IN CLINICAL TRIALS OF PREVENTIVE HIV VACCINES,” J Acquir Immune Defic Syndr Hum Retrovirol 12:406-412; Sheon, A. R. et al. (1998) “PREVENTING DISCRIMINATION AGAINST VOLUNTEERS IN PROPHYLACTIC HIV VACCINE TRIALS: LESSONS FROM A PHASE II TRIAL,” J Acquir Immune Defic Syndr Hum Retrovirol 19:519-526; Koblin, B. A. et al. (1998) “READINESS OF HIGH-RISK POPULATIONS IN THE HIV NETWORK FOR PREVENTION TRIALS TO PARTICIPATE IN HIV VACCINE EFFICACY TRIALS IN THE UNITED STATES,” Aids 12:785-793. Currently, there is no HIV detection assay that differentiates between vaccine generated antibodies and those produced after true HIV infection during HIV vaccine trials.
HIV-2 (also known as the West African AIDS Virus) is closely related to the simian immunodeficiency virus, and infected individuals are found primarily in West Africa (Smith, R. S. et al. (1990) “SYNTHETIC PEPTIDE ASSAYS TO DETECT HUMAN IMMUNODEFICIENCY VIRUS TYPES 1 AND 2 IN SEROPOSITIVE INDIVIDUALS,” Arch Pathol Lab Med. 114(3):254-258; Baillou, A. et al. (1991) “FINE SEROTYPING OF HUMAN IMMUNODEFICIENCY VIRUS SEROTYPE 1 (HIV-1) AND HIV-2 INFECTIONS BY USING SYNTHETIC OLIGOPEPTIDES REPRESENTING AN IMMUNODOMINANT DOMAIN OF HIV-1 AND HIV-2/SIMIAN IMMUNODEFICIENCY VIRUS,” J Clin Microbiol. 29(7):1387-1391).
HIV acts to compromise the immune system of infected individuals by targeting and infecting the CD-4+T lymphocytes that would otherwise be the major proponents of the recipient's cellular immune system response (Dalgleish, A. et al. (1984) “THE CD4 (T4) ANTIGEN IS AN ESSENTIAL COMPONENT OF THE RECEPTOR FOR THE AIDS RETROVIRUS,” Nature 312: 767-768, Maddon et al. (1986) “THE T4 GENE ENCODES THE AIDS VIRUS RECEPTOR AND IS EXPRESSED IN THE IMMUNE SYSTEM AND THE BRAIN,” Cell 47:333-348; McDougal, J. S. et al. (1986) “BINDING OF HTLV-III/LAV TO T4+T CELLS BY A COMPLEX OF THE 110K VIRAL PROTEIN AND THE T4 MOLECULE,” Science 231:382-385). HIV infection is pandemic and HIV-associated diseases represent a major world health problem.
Infection of cells by HIV-1 requires membrane attachment of the virion and subsequent fusion of the viral and cellular membranes. The fusion process is mediated by the viral outer envelope glycoprotein complex (gp120/gp41) and target cell receptors (McGaughey, G. B. et al. (2004) “PROGRESS TOWARDS THE DEVELOPMENT OF A HIV-1 GP41-DIRECTED VACCINE,” Curr HIV Res. 2(2):193-204). The envelope glycoprotein is synthesized as a precursor protein (gp160) that is proteolytically cleaved into two non-covalently associated protein subunits, a surface subunit (gp120) and a transmembrane subunit (gp41). The gp120 envelope protein is responsible for binding to the CD4 cell-surface receptor and a chemokine co-receptor, CCR5 or CXCR4. Following receptor binding, the membrane-anchored gp41 mediates fusion of the viral and target cell membranes. The gp41 ectodomain contains a hydrophobic, glycine-rich fusion peptide (amino acids 512-527) at the amino terminus that is essential for membrane fusion (numbering based on HXB2 gp160 variant as described in Chan, D. C. et al. (1997) “CORE STRUCTURE OF GP41 FROM THE HIV ENVELOPE GLYCOPROTEIN,” Cell 89(2):263-273). Two 4,3 hydrophobic repeat regions following the fusion peptide are defined by a heptad repeat (abcdefg)n, where the residues occupying the a and d positions are predominantly hydrophobic. The two heptad repeat regions are referred to as the N36 (residues 546-581) and C34 (residues 628-661) peptides. A loop region containing a disulfide linkage separates the two heptad repeat regions. The region of the gp41 ectodomain proximal to the viral membrane is abundant in the amino acid tryptophan (amino acids 665-683) and has been shown to be critical for the membrane fusion mechanism of HIV-1. Gp41 exists in two distinct conformations, a native or non-fusogenic state and a fusion-active state (fusogenic state) (McGaughey, G. B. et al. (2004) “PROGRESS TOWARDS THE DEVELOPMENT OF A HIV-1 GP41-DIRECTED VACCINE,” Cuff HIV Res. 2(2):193-204). On the surface of free virions, gp41 exists in the native state with the N-terminal fusion peptide largely inaccessible. Following interaction of the gp120/gp41 complex with cell-surface receptors, gp41 undergoes a series of conformational changes leading to the fusion-active conformation (Chan, D. C. et al. (1998) HIV ENTRY AND ITS INHIBITION,” Cell 93(5):681-684). The transition from the native non-fusogenic to fusion-competent state proceeds through a nascent species termed the prehairpin intermediate. In this transient conformation, the N- and C-terminal regions of gp41 become separated; the N-terminal fusion peptide is inserted into the target cell membrane and the C-terminal region is anchored to the viral membrane. The prehairpin intermediate ultimately folds into the fusion-active confonnation bringing the viral and target membranes into proximity allowing viral entry into the target cell (Chan, D. C. et al. (1998) HIV ENTRY AND ITS INHIBITION,” Cell 93(5):681-684).
The detection of HIV infection may be accomplished by either identifying viral proteins in the sera of infected individuals, by identifying viral nucleic acids in plasma or cells, or by detecting host antibodies that are produced by such individuals in response to viral infection. Strategies involving the detection of viral proteins are complicated by the low levels of such proteins during HIV infection, and by high assay cost. Thus, the detection of HIV infection is typically accomplished by detecting host anti-HIV antibodies (Manocha, M. et al. (2003) “COMPARING MODIFIED AND PLAIN PEPTIDE LINKED ENZYME IMMUNOSORBENT ASSAY (ELISA) FOR DETECTION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) AND TYPE-2 (HIV-2) ANTIBODIES,” Immunol Lett. 85(3):275-278). Such detection is however, complicated by the etiology of HIV infection, in which a significant initial “eclipse” period precludes detection of elicited antibodies (Mortimer, P. P. (1991) “THE FALLIBILITY OF HIV WESTERN BLOT,” Lancet 11:286-286), and by persistant false positive results (Gnann, J. W. Jr. et al. (1989) “CUSTOM-DESIGNED SYNTHETIC PEPTIDE IMMUNOASSAYS FOR DISTINGUISHING HIV TYPE 1 AND TYPE 2 INFECTIONS,” Methods Enzymol. 178:693-714). Due to these problems, more sensitive and expensive tests, such as the Western blot are often needed to confirm positive screening test results or to detect low level of circulating virus. However, Western blot analyses sometimes give indeterminate results so that a combination of screening tests (ELISA or Rapid tests) is required to confirm the diagnosis (Mortimer, P. P. (1991) “THE FALLIBILITY OF HIV WESTERN BLOT,” Lancet 11:286-286; Brattegaard, K. et al. (1995) “INSENSITIVITY OF A SYNTHETIC PEPTIDE-BASED TEST (PEPTI-LAV 1-2) FOR THE DIAGNOSIS OF HIV INFECTION IN AFRICAN CHILDREN,” AIDS 9(6):656-657). Additionally, different HIV proteins are expressed at different times during infection. For example, the env-gene products of HIV have been found to induce an immune response that precedes the immune response of HIV's gag-related gene products (Döpel, S. H. et al. (1991) “COMPARISON OF FOUR ANTI-HIV SCREENING ASSAYS WHICH BELONG TO DIFFERENT TEST GENERATIONS,” Eur. J. Clin. Chem. Clin. Biochem. 29:331-337).
The most common screening method for the diagnosis of infection with human immunodeficiency virus (HIV) is the detection (by sandwich ELISA) of virus-specific antibodies elicted by infected individuals in response to the infection (Döpel, S. H. et al. (1991) “COMPARISON OF FOUR ANTI-HIV SCREENING ASSAYS WHICH BELONG TO DIFFERENT TEST GENERATIONS,” Eur. J. Clin. Chem. Clin. Biochem. 29:331-337; Manocha, M. et al. (2003) “COMPARING MODIFIED AND PLAIN PEPTIDE LINKED ENZYME IMMUNOSORBENT ASSAY (ELISA) FOR DETECTION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) AND TYPE-2 (HIV-2) ANTIBODIES,” Immunol Lett. 85(3):275-278; Alcaro, M. C. et al. (2003) “SYNTHETIC PEPTIDES IN THE DIAGNOSIS OF HIV INFECTION,” Curr Protein Pept Sci. 4(4):285-290; Beristain, C. N. et al. (1995) “EVALUATION OF A DIPSTICK METHOD FOR THE DETECTION OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION,” J. Clin. Lab. Anal. 9(6):347-350). “First generation” assays used purified viral proteins obtained from infected cells to bind, and identify, such antibodies. However, since diagnostically relevant viral proteins, such as those encoded by the HIV-1 env gene were difficult to obtain in large quantities, “second generation” assays were soon developed that employed recombinantly produced HIV antigens.
Unfortunately, the use of such recombinant products requires extensive protein purification in order to avoid false positive results. Thus, it has been proposed that synthetic peptides be used to bind to and detect HIV-1 antibodies (Döpel, S. H. et al. (1991) “COMPARISON OF FOUR ANTI-HIV SCREENING ASSAYS WHICH BELONG TO DIFFERENT TEST GENERATIONS,” Eur. J. Clin. Chem. Clin. Biochem. 29:331-337; Manocha, M. et al. (2003) “COMPARING MODIFIED AND PLAIN PEPTIDE LINKED ENZYME IMMUNOSORBENT ASSAY (ELISA) FOR DETECTION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) AND TYPE-2 (HIV-2) ANTIBODIES,” Immunol Lett. 85(3):275-278; Alcaro, M. C. et al. (2003) “SYNTHETIC PEPTIDES IN THE DIAGNOSIS OF HIV INFECTION,” Curr Protein Pept Sci. 4(4):285-290; Baillou, A. et al. (1991) “FINE SEROTYPING OF HUMAN IMMUNODEFICIENCY VIRUS SEROTYPE 1 (HIV-1) AND HIV-2 INFECTIONS BY USING SYNTHETIC OLIGOPEPTIDES REPRESENTING AN IMMUNODOMINANT DOMAIN OF HIV-1 AND HIV-2/SIMIAN IMMUNODEFICIENCY VIRUS,” J Clin Microbiol. 29(7):1387-1391; Gnann, J. W. Jr. et al. (1989) “CUSTOM-DESIGNED SYNTHETIC PEPTIDE IMMUNOASSAYS FOR DISTINGUISHING HIV TYPE 1 AND TYPE 2 INFECTIONS,” Methods Enzymol. 178:693-714; Beristain, C. N. et al. (1995) “EVALUATION OF A DIPSTICK METHOD FOR THE DETECTION OF HUMAN IMMUNODEFICIENCY VIRUS INFECTION,” J Clin Lab Anal. 1995; 9(6):347-350; Modrow, S. et al. (1989) “CARRIER BOUND SYNTHETIC OLIGOPEPTIDES IN ELISA TEST SYSTEMS FOR DISTINCTION BETWEEN HIV-1 AND HIV-2 INFECTION,” J Acquir Immune Defic Syndr. 2(2):141-148; Smith, R. S. et al. (1990) “SYNTHETIC PEPTIDE ASSAYS TO DETECT HUMAN IMMUNODEFICIENCY VIRUS TYPES 1 AND 2 IN SEROPOSITIVE INDIVIDUALS,” Arch Pathol Lab Med. 114(3):254-258).
Synthetic peptide antigens coupled with ELISA offers several potential advantages over other types of assays, potentially increasing the sensitivity and specificity of the assay, decreasing its cost, and providing a relatively simple format that would be suitable for testing sizeable number of samples in any laboratory (Manocha, M. et al. (2003) “COMPARING MODIFIED AND PLAIN PEPTIDE LINKED ENZYME IMMUNOSORBENT ASSAY (ELISA) FOR DETECTION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE-1 (HIV-1) AND TYPE-2 (HIV-2) ANTIBODIES,” Immunol Lett. 85(3):275-278). Additionally, such peptides, if they elicit antibody formation, could be used as an anti-HIV vaccine (Petrov, R. V. et al. (1990) “THE USE OF SYNTHETIC PEPTIDES IN THE DIAGNOSIS OF HIV INFECTIONS,” Biomed Sci. 1(3):239-244).
Suitable synthetic peptides comprise short protein sequences that can be recognized by antibodies that have been elicited through an individual's exposure to the intact viral protein (Alcaro, M. C. et al. (2003) “SYNTHETIC PEPTIDES IN THE DIAGNOSIS OF HIV INFECTION,” Curr Protein Pept Sci. 4(4):285-290). In particular, it has been proposed that such peptides must possess the following characteristics: (1) an ability to detect an antibody response in all HIV-infected individuals; (2) an ability to detect an antibody response as early as possible after infection; and (3) an ability to maintain detection of antibody response over all stages of the disease (Döpel, S. H. et al. (1991) “COMPARISON OF FOUR ANTI-HIV SCREENING ASSAYS WHICH BELONG TO DIFFERENT TEST GENERATIONS,” Eur. J. Clin. Chem. Clin. Biochem. 29:331-337; Döpel, S. H. et al. (1990) “FINE MAPPING OF AN IMMUNODOMINANT REGION OF THE TRANSMEMBRANE PROTEIN OF THE HUMAN IMMUNODEFICIENCY VIRUS (HIV-1),” J. Virol. Meth. 25:167-178; Alcaro, M. C. et al. (2003) “SYNTHETIC PEPTIDES IN THE DIAGNOSIS OF HIV INFECTION,” Curr Protein Pept Sci. 4(4):285-290). In particular, the HIV-1 p24 (gag) protein, gp160/120 (env) protein and gp41 (env envelope transmembrane protein) have been proposed as having serodiagnostic importance, and as being a potential source of suitable peptides (Alcaro, M. C. et al. (2003) “SYNTHETIC PEPTIDES IN THE DIAGNOSIS OF HIV INFECTION,” Curr Protein Pept Sci. 4(4):285-290).
Additionally, it is important to be able to distinguish between the HIV-1 and HIV-2 variants of HIV (Smith, R. S. et al. (1990) “SYNTHETIC PEPTIDE ASSAYS TO DETECT HUMAN IMMUNODEFICIENCY VIRUS TYPES 1 AND 2 IN SEROPOSITIVE INDIVIDUALS,” Arch Pathol Lab Med. 114(3):254-258; Baillou, A. et al. (1991) “FINE SEROTYPING OF HUMAN IMMUNODEFICIENCY VIRUS SEROTYPE 1 (HIV-1) AND HIV-2 INFECTIONS BY USING SYNTIIETIC OLIGOPEPTIDES REPRESENTING AN IMMUNODOMINANT DOMAIN OF HIV-1 AND HIV-2/SIMIAN IMMUNODEFICIENCY VIRUS,” J Clin Microbiol. 29(7):1387-1391; Modrow, S. et al. (1989) “CARRIER BOUND SYNTHETIC OLIGOPEPTIDES IN ELISA TEST SYSTEMS FOR DISTINCTION BETWEEN HIV-1 AND HIV-2 INFECTION,” J Acquir Immune Defic Syndr. 2(2):141-148). These variants share 40-60% homology at the amino acid level (Alcaro, M. C. et al. (2003) “SYNTHETIC PEPTIDES IN THE DIAGNOSIS OF HIV INFECTION,” Curr Protein Pept Sci. 4(4):285-290; Gueye-Ndiaye, A. et al. (1993) “COST-EFFECTIVE DIAGNOSIS OF HIV-1 AND HIV-2 BY RECOMBINANT-EXPRESSED ENV PEPTIDE (566/996) DOT-BLOT ANALYSIS,” AIDS. 7(4):475-481).
Methods for detecting HIV or other viral pathogens are disclosed in WO9008162A1, and in U.S. Pat. Nos. 6,689,879; 6,649,749; 6,623,920; 6,589,734; 6,586,177; 6,582,920; 6,541,609; 6,534,285; 6,531,276; 6,492, 104; 6,458,527; 6,399,307; 6,352,826; 6,270,959; 6,252,059; 6,245,737; 6,048,685; 6,008,044; 5,928,642; 5,925,513; 5,891,623; 5,856,088; 5,849,494; 5,830,641; 5,721,095; 5,712,385; 5,705,331; 5,695,930; 5,681,696; 5,660,979; 5,637,453; 5,599,662; 5,476,765; 5,462,852; 5,459,060; 5,260,189; and in European Patent Documents EP0439077B1, EP0439077A2.
Substantial progress has been made in the management and treatment of HIV-1 infection. However, available antiretroviral therapies can cause metabolic toxicity (Sommerfelt, M. A. et al. (2004) “NOVEL PEPTIDE-BASED HIV-1 IMMUNOTHERAPY,” Expert Opin Biol Ther. 4(3):349-61), and thus alternative strategies to control HIV-1 infection are needed (McGaughey, G. B. et al. (2004) “PROGRESS TOWARDS THE DEVELOPMENT OF A HIV-1 GP41-DIRECTED VACCINE,” Curr HIV Res. 2(2):193-204). The use of peptide immunogens has been proposed as the basis for an anti-HIV-1 vaccine (Sommerfelt, M. A. et al. (2004) “NOVEL PEPTIDE-BASED HIV-1 IMMUNOTHERAPY,” Expert Opin Biol Ther. 4(3):349-61; Berzofsky, J. A. et al. (1995) “NOVEL APPROACHES TO PEPTIDE AND ENGINEERED PROTEIN VACCINES FOR HIV USING DEFINED EPITOPES: ADVANCES IN 1994-1995,” AIDS 9 Suppl A:S143-157; Choppin, J. et al. (2001) “CHARACTERISTICS OF HIV-1 NEF REGIONS CONTAINING MULTIPLE CD8+T CELL EPITOPES: WEALTH OF HLA-BINDING MOTIFS AND SENSITIVITY TO PROTEASOME DEGRADATION,” J Immunol. 166(10):6164-6169; Berzofsky, J. A. et al. (1999) “APPROACHES TO IMPROVE ENGINEERED VACCINES FOR HUMAN IMMUNODEFICIENCY VIRUS AND OTHER VIRUSES THAT CAUSE CHRONIC INFECTIONS,” lmmunol Rev. 170:151-172; Cho, M. W. (2003) “SUBUNIT PROTEIN VACCINES: THEORETICAL AND PRACTICAL CONSIDERATIONS FOR HIV-1,” Curr Mol Med. 3(3):243-263; Sabatier, J. M. et al. (1989) “USE OF SYNTHETIC PEPTIDES FOR THE DETECTION OF ANTIBODIES AGAINST THE NEF REGULATING PROTEIN IN SERA OF HIV-INFECTED PATIENTS,” AIDS. 3(4):215-220; van der Ryst, E. (2002) “PROGRESS IN HIV VACCINE RESEARCH,” Oral Dis. 8 Suppl 2:21-26; Zolla-Pazner, S. (2004) “IDENTIFYING EPITOPES OF HIV-1 THAT INDUCE PROTECTIVE ANTIBODIES,” Nat Rev Immunol. 4(3):199-210.
Unfortunately, the identification of suitable peptides is encumbered by the rapid mutation and recombination exhibited by retroviruses, extreme variability is found in HIV proteins. Although conserved regions in HIV-1 gp120 (residues 495-516), gp41 (residues 67-83 and 584-618), and gp36 (residues 574-602) have been investigated as potential sequences for candidate peptides (Alcaro, M. C. et al. (2003) “SYNTHETIC PEPTIDES IN THE DIAGNOSIS OF HIV INFECTION,” Curr Protein Pept Sci. 4(4):285-290), prior efforts to define suitable peptides have not been fully satisfactory. Petrov, R. V. et al. disclose that many candidate peptides failed to identify HIV infection in HIV-infected individuals, necessitating the use of multiple peptides in order to detect HIV infection (Petrov, R. V. et al. (1990) “THE USE OF SYNTHETIC PEPTIDES IN THE DIAGNOSIS OF HIV INFECTIONS,” Biomed Sci. 1(3):239-244). Thus, an important problem facing the field of HIV diagnostics is the identification of a suitable peptide that would be recognized broadly, or universally, by the full range of clinically identified HIV variants. Likewise, at present no identified peptide has resulted in an HIV-1 immunotherapy that could be used as the basis for a vaccine that would provide substantial or full immunoprotection to infection by such variants (Sommerfelt, M. A. et al. (2004) “NOVEL PEPTIDE-BASED HIV-1 IMMUNOTHERAPY,” Expert Opin Biol Ther. 4(3):349-61). In addition, suitable diagnostic tests should be able to distinguish between individuals whose sera contain anti-HIV antibodies as a result of their receipt of an anti-HIV vaccine and individuals whose sera contain anti-HIV antibodies as a result of HIV infection. The present invention is directed to this and other needs.